Mediation of Neuronal Apoptosis by Kv2.1-Encoded Potassium Channels

• Published in: The Journal of neuroscience Vol. 23; no. 12; pp. 4798 - 4802
• Main Authors: Pal, Sumon, Hartnett, Karen A, Nerbonne, Jeanne M, Levitan, Edwin S, Aizenman, Elias
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 15.06.2003; Society for Neuroscience
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Brief Communications; Cells, Cultured; CHO Cells; Cricetinae; Cytoprotection - genetics; Cytoprotection - physiology; Delayed Rectifier Potassium Channels; Genes, Dominant; Neurons - cytology; Neurons - metabolism; Oxidants - toxicity; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Voltage-Gated; Protein Subunits - genetics; Protein Subunits - metabolism; Rats; Shab Potassium Channels; Signal Transduction - drug effects; Signal Transduction - physiology; Staurosporine - toxicity; Transfection
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.23-12-04798.2003

Cellular K+ efflux is a requisite event in the unfolding of apoptosis programs across many types of cells and death-inducing stimuli; however, the molecular identities of the ion channels mediating this key event have remained undefined. Here, we show that Kv2.1-encoded K+ channels are responsible for the expression of apoptosis in cortical neurons in vitro. Transient expression of two different dominant-negative forms of this subunit in neurons completely eliminated the enhancement of K+ currents that normally accompanies the cell death process. Importantly, neurons deficient in functional Kv2.1-encoded K+ channels were protected from oxidant and staurosporine-induced apoptosis. Finally, Chinese hamster ovary cells, which do not express endogenous voltage-gated K+ channels, became substantially more sensitive to apoptosis after transient expression of wild-type Kv2.1. These results suggest that Kv2.1-encoded K+ channels are necessary for the apoptotic signaling cascade in mammalian cortical neurons in culture and are sufficient for increasing the susceptibility to apoptogens in a nonexcitable cell.